基于网络药理学探讨鬼针草治疗血脂异常的作用机制

Discussion on the Mechanism of Bidens in Treatment of Dyslipidemia Based on Network Pharmacology

摘要: 目的：基于网络药理学探讨鬼针草治疗血脂异常的有效活性成分及作用机制。方法：通过中药系统药理学数据库(traditional Chinese medicine systems pharmacology database and analysis platform, TCMSP)检索鬼针草有效成分及靶点；利用GeneCards和DisGeNET数据库获取血脂异常疾病靶点；应用Venny2.1.0导入鬼针草和血脂异常靶点获得交集基因靶点，将交集靶点导入STRING数据库构建鬼针草–血脂异常蛋白相互作用(PPI)网络；利用Cytoscape3.7.2软件绘制前10核心靶点图，用Tools工具对鬼针草–有效成分–共同靶点–血脂异常相互关系进行可视化分析；采用DAVID数据库进行基因本体论(gene ontology, GO)和京都基因与基因组百科全书(KEGG)通路富集分析，OmicShare Tools云工具绘制GO富集和KEGG通路高级气泡图。结果：共筛选鬼针草有效成分6个及靶点144个，血脂异常疾病靶点3846个，共同交集基因靶点119个；共靶点GO富集分析，共获得732条GO注释(P < 0.01)，其中573条与生物过程有关、46条与细胞组分有关，113条与分子功能有关；共靶点KEGG通路分析，共获得113条KEGG信号通路(P < 0.01)；根据P值大小筛选前20进行可视化。结论：鬼针草可能是通过AKT1、TNF、IL6等关键基因靶点，参与细胞对脂多糖的反应、基因表达的正调控、炎症反应等生物过程，经肿瘤坏死因子信号通路、HIF-1信号通路、Toll样受体信号通路等发挥治疗血脂异常及动脉粥样硬化心血管疾病(ASCVD)的作用。

Abstract: Objective: To explore the effective active ingredients and mechanism of Bidens in the treatment of dyslipidemia based on network pharmacology. Methods: Search the active ingredients and targets of Bidens through the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP); Use GeneCards and DisGeNET databases to obtain dyslipidemia disease targets; Use Venny2.1.0 to import Bidens and dyslipidemia targets to obtain the intersection gene targets, and import the intersection targets into the STRING database to construct the Bidens-Dyslipidemia Protein Interaction (PPI) network; Use Cytoscape3.7.2 software to draw the top 10 core target map, and use Tools to visually analyze the relationship between Bidens-active ingredients-common targets-dyslipidemia; The DAVID database was used for gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis, OmicShare Tools cloud tool draws GO enrichment and KEGG pathway high-level bubble maps. Results: A total of 6 active ingredients and 144 targets of Bidens were screened, 3846 targets for dyslipidemia diseases, and 119 common genetic targets were intersected; Co-targeted GO enrichment analysis, 732 GO annotations (P < 0.01) were obtained, of which 573 were related to biological processes, 46 were related to cell components, and 113 were related to molecular functions; Co-target KEGG pathway analysis, a total of 113 KEGG signal pathways were obtained (P < 0.01); Filter the top 20 according to the size of the P value for visualization. Conclusion: Bidens may be through AKT1, TNF, IL6, etc. key gene targets, to participate in cellular response to lipopolysaccharide, positive regulation of gene expression, inflammatory response, etc. biological processes, through the tumor necrosis factor signaling pathway, HIF-1 signaling pathway, Toll-like receptor signaling pathway, etc. for the treatment of dyslipidemia and atherosclerotic cardiovascular disease (ASCVD).